Osteoimmunology (όστέον, ''osteon'' from Greek, "bone"; from Latin, "immunity"; and λόγος, ''logos'', from Greek "study") is a field that emerged about 40 years ago that studies the interface between the

skeletal system A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fra ...

and the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

, comprising the "osteo-immune system". Osteoimmunology also studies the shared components and mechanisms between the two systems in vertebrates, including ligands, receptors, signaling molecules and transcription factors. Over the past decade, osteoimmunology has been investigated clinically for the treatment of bone metastases,

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

(RA),

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

osteopetrosis Osteopetrosis, literally , also known as marble bone disease or Albers-Schönberg disease, is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which ...

, and

periodontitis Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main c ...

. Studies in osteoimmunology reveal relationships between molecular communication among blood cells and structural pathologies in the body.

System similarities

The

RANKL Receptor activator of nuclear factor kappa- ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiat ...

RANK A rank is a position in a hierarchy. It can be formally recognized—for example, cardinal, chief executive officer, general, professor—or unofficial. People Formal ranks * Academic rank * Corporate title * Diplomatic rank * Hierarchy ...

- OPG axis (OPG stands for osteoprotegerin) is an example of an important signaling system functioning both in

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

and immune cell communication. RANKL is expressed on

osteoblast Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...

s and activated

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s, whereas RANK is expressed on

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

s, and

dendritic cell A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

s (DCs), both of which can be derived from

myeloid Myeloid tissue, in the bone marrow sense of the word '' myeloid'' ('' myelo-'' + '' -oid''), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (''myelo-'' + '' -genous'') is any tissue ...

progenitor cells. Surface RANKL on osteoblasts as well as secreted RANKL provide necessary signals for osteoclast precursors to differentiate into osteoclasts. RANKL expression on activated T cells leads to DC activation through binding to RANK expressed on DCs. OPG, produced by DCs, is a soluble decoy receptor for RANKL that competitively inhibits RANKL binding to RANK.

Crosstalk

The

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

cavity is important for the proper development of the immune system, and houses important stem cells for maintenance of the immune system. Within this space, as well as outside of it,

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s produced by immune cells also have important effects on regulating bone homeostasis. Some important cytokines that are produced by the immune system, including RANKL, M-CSF, TNFa, ILs, and IFNs, affect the differentiation and activity of osteoclasts and

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nuclea ...

. Such inflammatory osteoclastogenesis and osteoclast activation can be seen in ex vivo primary cultures of cells from the inflamed

synovial fluid Synovial fluid, also called synovia, elp 1/sup> is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articul ...

of patients with disease flare of the autoimmune disease rheumatoid arthritis.

Clinical osteoimmunology

Clinical osteoimmunology is a field that studies a treatment or prevention of the bone related diseases caused by disorders of the immune system. Aberrant and/or prolonged activation of immune system leads to derangement of bone modeling and remodeling. Common diseases caused by disorder of osteoimmune system is

and bone destruction accompanied by RA characterized by high infiltration of CD4+ T cells in rheumatoid joints, in which two mechanisms are involved: One is an indirect effect on osteoclastogenesis from rheumatoid synovial cells in joints since synovial cells have osteoclast precursors and osteoclast supporting cells, synovial macrophages are highly differentiated into osteoclasts with help of RANKL released from osteoclast supporting cells. The second is an indirect effect on osteoclast differentiation and activity by the secretion of inflammatory cytokines such as IL-1, IL-6, TNFa, in synovium of RA, which increase RANKL signaling and finally bone destruction. A clinical approach to prevent bone related diseases caused by RA is OPG and RANKL treatment in arthritis. There is some evidence that infections (e.g. respiratory virus infection) can reduce the numbers of osteoblasts in bone, the key cells involved in bone formation.

References

{{Reflist Physiology Branches of immunology

System similarities

Crosstalk

Clinical osteoimmunology

See also

References